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PubMed2004

Reversion of hypertrophic cardiomyopathy in a patient with deficiency of the mitochondrial copper binding protein Sco2: is there a potential effect of copper?

Mutations in Sco2, a protein involved in copper trafficking to the terminal enzyme of the respiratory chain, cytochrome c oxidase, results in infantile hypertrophic cardioencephalomyopathy. We have recently shown that copper-histidine (Cu-his) supplementation of Sco2-deficient myoblasts rescues COX activity in vitro. Here, we report a patient with SCO 2 mutations and with resolution of severe hypertrophic cardiomyopathy. Weighing up the evidence, the most likely explanation for the improved cardiac function in this patient was the subcutaneous application of Cu-his.

Cardiomyopathy, Hypertrophic↗
PubMed2003

Catena-poly[[trans-bis(ethane-1,2-diamine-kappa2N,N')copper(II)]-micro-dithionato-kappa2O:O'] and trans-diaquabis(propane-1,3-diamine-kappa2N,N')copper(II) dithionate.

In title anhydrous catena-poly[[trans-bis(ethane-1,2-diamine-kappa(2)N,N')copper(II)]-micro-dithionato-kappa(2)O:O'], [Cu(S(2)O(6))(C(2)H(8)N(2))(2)](n) or [[H(2)N(CH(2))(2)NH(2)](2)Cu(O.O(2)SSO(2).O)]( infinity ), successive Cu atoms are bridged by a single doubly charged dithionate group, forming a one-dimensional polymer with inversion centres at the metal atoms and the mid-point of the S-S bond [Cu-O = 2.5744 (15) A]. In title (hydrated) trans-diaquabis(propane-1,3-diamine-kappa(2)N,N')copper(II) dithionate, [Cu(C(3)H(10)N(2))(2)(H(2)O)(2)](S(2)O(6)) or [[H(2)N(CH(2))(3)NH(2)](2)Cu(OH(2))(2)](S(2)O(6)), both ions have imposed 2/m symmetry. The 'axial' anion components are displaced by a pair of water ligands [Cu-O = 2.439 (3) A], the shorter Cu-O distance being compensated by the lengthened Cu-N distance [2.0443 (18), cf. 2.0100 (13) and 2.0122 (16) A].

Journal Article↗
PubMed2004

Di-mu-hydroxo-bis[aqua(1,10-phen-anthroline-kappa2N,N')copper(II)] trans-bis(2-([(E)-5-formyl-2-oxido-kappaO-benzylidene]amino-kappaN)ethanesulfonato(2-))copper(II) hexahydrate.

The title compound, [Cu(2)(OH)(2)(C(12)H(8)N(2))(2)(H(2)O)(2)][Cu(C(10)H(9)NO(5)S)(2)].6H(2)O, is comprised of a copper-centred complex cation and a copper-centred complex anion; the cation lies about an inversion centre and in the anion the Cu atom lies on an inversion centre. In the doubly charged bridged dicopper cation, each Cu centre has distorted square-pyramidal geometry. In the square-planar dianion, two sulfonate ligands are trans coordinated to the Cu atom via a deprotonated hydroxyl O atom and an imine N atom, forming two six-membered chelate rings. The structure is stabilized by an extensive hydrogen-bond system and aromatic-ring stacking interactions.

Journal Article↗
PubMed2005

Tetrakis(1-ethyl-1H-1,2,4-triazole-kappaN4)bis(nitrato-kappaO)copper(II) and bis(nitrato-kappaO)tetrakis(1-propyl-1H-1,2,4-triazole-kappaN4)copper(II).

The copper(II) environments for tetrakis(1-ethyl-1,2,4-triazole)dinitratocopper(II), [Cu(NO3)2(C4H7N3)4], and tetrakis(1-propyl-1,2,4-triazole)dinitratocopper(II), [Cu(NO3)2(C5H9N3)4], are distorted square bipyramidal. Both structures are centrosymmetric, with the copper(II) ions located at inversion centers coordinated by four N atoms of four triazole molecules and by two O atoms of two nitrate ions in an elongated octahedral geometry. This elongation is a result of the Jahn-Teller effect. The largest distortion is that of the N-Cu-O angles, which differ from 90 degrees by 5.68 (10) degrees in the ethyl and 5.59 (8) degrees in the propyl derivative.

Journal Article↗
PubMed1997

Bacterial community in copper sulfide ores inoculated and leached with solution from a commercial-scale copper leaching plant.

Most copper bioleaching plants operate with a high concentration of sulfate salts caused by the continuous addition of sulfuric acid and the recycling of the leaching solution. Since the bacteria involved in bioleaching have been generally isolated at low sulfate concentrations, the bacterial population in ores leached with the high-sulfate solution (1.25 M) employed in a copper production plant was investigated. The complexity of the original population was assessed by the length pattern of the spacer regions between the 16S and 23S rRNA genes, observed after PCR amplification of the DNA extracted from the leached ore. Six main spacers were distinguished by electrophoretic migration, but they could be further resolved into eight spacers by nucleotide sequence homology. The degree of homology was inferred from the electrophoretic migration of the heteroduplexes formed after hybridization. One of the spacers was indistinguishable from that found in Thiobacillus thiooxidans, four could be related to Thiobacillus ferrooxidans, and three could be related to Leptospirillum ferrooxidans. Only five of the spacers in the original sample could be recovered after culturing in media containing different inorganic energy source. Altogether, the results indicate that the bacteria in the leached ore formed a community composed of at least three species: a fairly homogeneous population of T. thiooxidans strains and two heterogeneous populations of T. ferrooxidans and L. ferrooxidans strains.

Journal Article↗
PubMed1987

The blue copper protein gene of Alcaligenes faecalis S-6 directs secretion of blue copper protein from Escherichia coli cells.

The gene encoding a blue copper protein (a member of the pseudoazurins) of 123 amino acid residues, containing a single type I Cu2+ ion, was cloned from Alcaligenes faecalis S-6. The nucleotide sequence of the coding region, as well as the 5'- and 3'-flanking regions, was determined. The deduced amino acid sequence after Glu-24 coincided with the reported sequence of the blue protein, and its NH2-terminal sequence of 23 residues resembled a typical signal peptide. The cloned gene was expressed under the control of the tac promoter in Escherichia coli, and the correctly processed blue protein was secreted into the periplasm. The blue protein produced in E. coli possessed the activity to transfer electrons to the copper-containing nitrite reductase of A. faecalis S-6 in vitro.

Alcaligenes↗
PubMedDate not supplied

The antiproliferative agents trans-bis(resorcylaldoximato)copper(II) and trans-bis(2,3,4-trihydroxybenzaldoximato)copper(II) and cytopathic effects of HIV.

trans-Bis(resorcylaldoximato)copper(II) and trans-bis-(2,3,4-trihydroxybenzaldoximato)copper(II) (CuRES2 and CuTRI2, respectively) have been tested for antiviral properties against HIV, using an in vitro assay that measures the ability of the test compounds to prevent the killing of susceptible human cells by HIV. In the case of CuTRI2, T4 lymphocytes (CEM-V and CEM-Z cell lines) were exposed to HIV at a virus to cell ratio approx. 0.05 in microtiter plates. In the case of CuRES2, a human leukemia cell line (MT-2) was used instead. The tetrazolium salt XTT was added to all wells, and the cultures were incubated and analyzed spectrophotometrically to quantitate formazan production and viewed microscopically for detection of viable cells. In spite of their antiproliferative properties, neither agent had any detectable ability to prevent the cytopathic effects of HIV in cultures of the target cells used. Because the test system employed was constructed in such a way as to detect antiviral agents acting at any stage of the virus reproductive cycle, the results obtained strongly suggest that neither studied agent has any value as the direct prevention of the cell destruction caused by HIV is concerned.

Anti-HIV Agents↗
PubMed1992

[Studies on the analysis of copper chlorophyll and sodium copper chlorophyllin in imported foods].

The analysis of copper chlorophyll (CuCh) and sodium copper chlorophyllin (CuCh-Na) in imported foods was carried out. Standards of CuCh and CuCh-Na were examined by ultraviolet and visible spectrophotometer. CuCh gave absorption maximum around 650 nm, while CuCh-Na gave around 630 nm. Imported sweets and liqueurs were homogenized and extracted with ethyl acetate. These extracts also gave absorption maxima absorbance around 650 nm or 630 nm. The results suggested that a distinction between CuCh and CuCh-Na in foods was possible by spectrophotometry. Visible spectrophotometric quantitation was also tried. However the estimated levels of CuCh or CuCh-Na in the samples by this method did not meet with those by atomic absorption spectrometry.

Chlorophyllides↗
PubMed1988

Effect of copper fluoride and copper sulfate on dental plaque, Streptococcus mutans and caries in hamsters.

Topical applications of 10 mM CuF2, 10 mM CuSO4, or 20 mM NaF solutions were performed twice a day in hamsters infected with S. mutans and maintained on a high sucrose diet. Animals receiving the copper compounds exhibited lower plaque scores than control animals or animals treated with the NaF solution. The group receiving the CuF2 solution showed a lower number of S. mutans and a higher caries reduction than the groups treated with NaF or the non-fluoride compound CuSO4.

Animals↗
PubMed2000

[Biological regulation of copper and selective removal of copper: therapy for Wilson disease and its molecular mechanism].

Copper (Cu) is an essential trace element and constitutes the active center of the redox Cu enzymes such as Cu, Zn-superoxide dismutase (Cu, Zn-SOD), ceruloplasmin and cytochrome c oxidase. Among hereditary diseases due to a defect in the metabolism of Cu, Menkes disease (caused by a Cu deficiency) and Wilson disease (caused by the excessive accumulation of Cu) have been shown to be caused by the mutation of genes encoding Cu-binding ATPase for the efflux of Cu, ATP7A and ATP7B, respectively. Following the identification of these causative genes, intracellular Cu transporters (Cu chaperones) specific for the Golgi apparatus, mitochondria and Cu, Zn-SOD were discovered, and these findings have facilitated the study of the underlying mechanisms of the biological regulation of Cu. Apart from these physiological and biochemical studies, toxicological studies have elucidated the underlying mechanisms of the occurrence of acute hepatitis caused by the accumulation of Cu accumulating in the liver of an animal model for Wilson disease, LEC rats. In these toxicological studies, two biological aspects of metallothionein (MT), i.e., antioxidant and prooxidant depending on the Cu/Zn ratio in Cu-containing MT have been proposed. The present article overviews the recent findings on the biological regulation of Cu and on the toxicological aspect of Cu. It is known that Cu forms a stable ternary complex with molybdenum and sulfur under reductive conditions in the body. On the basis of this observation, tetrathiomolybdate (TTM) has been applied to remove Cu from the liver of Long-Evans rats with a cinnamon-like coat color (LEC) rats. Precise mechanisms underlying the complex formation between Cu bound to MT and TTM were presented, and an appropriate protocol for the chelation therapy was also proposed together with the mechanisms underlying the occurrence of side-effects.

Adenosine Triphosphatases↗
PubMed2000

Effects of dietary copper concentration and source on performance and copper status of growing and finishing steers.

Performance and Cu status were measured in growing and finishing steers supplemented with different copper (Cu) concentrations and sources. Sixty Angus (n = 36) and Angus x Hereford (n = 24) steers were stratified by weight and initial liver Cu concentration within a breed and randomly assigned to treatments. Treatments consisted of 1) control (no supplemental Cu); 2) 20 mg Cu/kg DM from Cu sulfate (CuSO4); 3) 40 mg Cu/kg DM from CuSO4; 4) 20 mg Cu/ kg DM from Cu citrate (C6H4Cu2O7); 5) 20 mg Cu/kg DM from Cu proteinate; and 6) 20 mg Cu/kg DM from tribasic Cu chloride (Cu2(OH)3Cl). A corn silage-soybean meal-based diet that was analyzed to contain 10.2 mg of Cu/kg DM was fed for 56 d. Steers were then switched to a high-concentrate diet that was analyzed to contain 4.9 mg of Cu/kg DM. Equal numbers of steers per treatment were slaughtered after receiving the finishing diets for either 101 or 121 d. Performance was not affected by Cu level or source during the growing phase. Gain, feed intake, and feed efficiency were reduced (P < .05) by Cu supplementation during the finishing phase. Plasma and liver Cu concentrations were higher in steers receiving supplemental Cu at the end of both the growing and finishing phases. Steers supplemented with 40 mg Cu/kg DM from CuSO4 had higher (P < .05) liver Cu concentrations than those supplemented with 20 mg Cu/kg DM from CuSO4. Liver Cu concentrations did not increase over the finishing phase relative to liver Cu concentrations at the end of the growing phase. These results indicate that as little as 20 mg/kg of supplemental Cu can reduce performance in finishing steers.

Animals↗
PubMed2004

Effect of dietary copper source (cupric citrate and cupric sulfate) and concentration on growth performance and fecal copper excretion in weanling pigs.

In each of two experiments, 924 pigs (4.99 kg BW; 16 to 18 d of age) were assigned to 1 of 42 pens based on BW and gender. Pens were allotted randomly to dietary copper (Cu) treatments that consisted of control (10 ppm Cu as cupric sulfate, CuSO4 x 5H2O) and supplemental dietary Cu concentrations of 15, 31, 62, or 125 ppm as cupric citrate (CuCit), or 62 (Exp. 2 only), 125 (Exp. 1 only), or 250 ppm as CuSO4. Live animal performance was determined at the end of the 45-d nursery phase in each experiment. On d 40 of Exp. 2, blood and fecal samples were collected from two randomly selected pigs per pen for evaluation of plasma and fecal Cu concentrations and fecal odor characteristics. In Exp. 1, ADG, ADFI, and G:F were increased (P < 0.05), relative to controls, when pigs were fed diets containing 250 ppm Cu as CuSO4. Pigs fed diets containing 125 ppm Cu as CuCit had increased (P < 0.05) ADG compared with pigs fed diets supplemented with 15 or 62 ppm Cu as CuCit. The ADG, ADFI, and G:F did not differ among pigs fed diets containing 125 and 250 ppm Cu as CuSO4 or 125 ppm Cu as CuCit. In Exp. 2, pigs fed diets containing 250 ppm Cu as CuSO4 had improved (P < 0.05) ADG, ADFI, and G:F compared with controls. In addition, ADG, ADFI, and G:F were similar when pigs were fed diets containing either 250 ppm Cu as CuSO4 or 125 ppm Cu as CuCit. Pigs fed diets containing 62 ppm Cu as CuSO4 or CuCit had similar ADG, ADFI, and G:F. Plasma Cu concentrations were not affected by dietary Cu source or concentration, but fecal Cu concentrations were increased (P < 0.05) as the dietary concentration of Cu increased. Pigs consuming diets supplemented with 125 ppm Cu as CuCit had fecal Cu concentrations that were lower (P < 0.05) than pigs consuming diets supplemented with 250 ppm Cu as CuSO4. Fecal Cu did not differ in pigs receiving diets supplemented with 62 ppm Cu as CuSO4 or CuCit. Odor characteristics of feces were not affected by Cu supplementation or source. These data indicate that 125 and 250 ppm Cu gave similar responses in growth, and that CuCit and CuSO4 were equally effective at stimulating growth and improving G:F in weanling pigs. Fecal Cu excretion was decreased when 125 ppm Cu as CuCit was fed compared with 250 ppm Cu as CuSO4. Therefore, 125 ppm of dietary Cu, regardless of source, may provide an effective environmental alternative to 250 ppm Cu as CuSO4 in weanling pigs.

Animal Feed↗
PubMed2002

Effect of copper source and level on the rate and extent of copper repletion in Holstein heifers.

The objective of this study was to evaluate the rate and extent of Cu repletion in Holstein heifers using two Cu sources (organic and inorganic) at two levels (15 and 30 mg/kg). An additional repletion treatment included a Cu oxide bolus. Heifers (n = 50) were individually fed a total mixed ration fortified with S and Mo at 0.40%, and 15 mg/kg of dry matter of the total diet, respectively. After 111 d of depletion, heifers were stratified by liver Cu concentration and randomly allotted to one of five repletion treatments. Four treatments consisted of feed sources of Cu (feed-Cu), 1) CuSO4 at 15 mg/kg; 2) CuSO4 at 30 mg/kg; 3) Availa-Cu at 15 mg/kg; and 4) Availa-Cu at 30 mg/kg. Availa-Cu is an organic Cu source that produces a Cu-amino acid complex. A fifth treatment, consisting of an intraruminal bolus (IB), provided a single dose of 25 g of CuO needles. Repletion treatments were delivered in the same total mixed ration without supplemental S and Mo. Copper status was assessed in blood and liver samples collected on 14-d intervals for 70 d. Irrespective of treatment, all heifers increased in body weight during the repletion period. Liver Cu increased in each feed-Cu treatment over time. Heifers treated with an IB reached a peak in liver Cu concentration (165.5 mg/kg) on d 28. Mean liver Cu concentrations were higher in heifers receiving 30 mg/kg of Cu compared with heifers receiving 15 mg/kg of Cu. Red blood cell superoxide dismutase (SOD) activity was higher (P < 0.001) in heifers receiving CuSO4 than Availa-Cu (0.98 vs 0.87 U). Also, SOD activity was higher when heifers were supplemented with 30 vs 15 mg/kg Cu (0.98 vs 0.87 U). Heifers receiving the Cu IB had higher SOD activity than heifers receiving feed-Cu sources (1.03 vs 0.92 U). Plasma ceruloplasmin concentration was higher (P < 0.001) in IB-treated heifers vs. other treatments. No differences in plasma ceruloplasmin were detected for feed-Cu source or level. These results indicate that all Cu sources evaluated in this study elevated Cu status of depleted heifers, particularly when provided at higher dietary levels.

Animals↗
PubMed1991

Effects of copper sources and dietary cation-anion balance on copper availability and acid-base status in dairy calves.

Twenty-four Holstein and Jersey calves (14 Holstein), 4 to 11 d of age, were assigned randomly to six treatments in a 2 x 3 factorial arrangement to examine the effects of Cu sources and dietary cation-anion balance on Cu availability and acid-base balance. Treatments were cationic basal diet (20 meq of dietary cation-anion balance on a DM basis), cationic basal diet supplemented with CuO, cationic basal diet supplemented with CuSO4, anionic basal diet (-10 meq), anionic basal diet supplemented with CuO, and anionic basal diet supplemented with CuSO4. Copper sources did not show any effect on growth of calves. The cationic diet increased calf growth compared with the anionic diet at wk 12 of the experiment. Blood pH was increased by the cationic diet in comparison with the anionic diet at wk 8 and 12. Blood pH also was increased by CuSO4 compared with CuO treatment in the early period of the treatment. Blood bicarbonate concentration was decreased by CuO and the anionic diet. Interactions between Cu sources and cation-anion balance were found for blood pH and bicarbonate concentration. Liver Cu concentration was increased by CuSO4 but not by CuO supplementation compared with control. Therefore, CuSO4 was found to be highly available, whereas CuO was a very poorly available source of Cu for young calves.

Acid-Base Equilibrium↗
PubMed2002

[Properties of chitosan and sorption of copper ions from a copper sulfate solution on chitosan].

The introduction of the paper briefly describes the properties of chitosan and the current utilization of the aminopolysaccharides chitosan, chitin, and their derivatives in pharmaceutical formulations, and in the health services also as sorbents of heavy metals and other substances. The degree of deacetylation (64%) of commercially produced chitosan was estimated from measured IR spectra, and spectrophotometry in the visible region was employed to study the kinetics and equilibrium of the Cu(II) ion sorption from CuSO4 aqueous solutions. Cu(II) sorption on the suspended chitosan was rather slow, it took 8-12 hrs to establish the sorption equilibrium, but the maximum determined sorption capacity, up to 200 mg of copper per 1 g of chitosan, greatly exceeded other adsorbents. A nearly stoichiometric ratio between the sorbed Cu(II) and the chitosan biopolymer structural units as well as decreasing sorption at lower pH (4-5) suggests complex formation of Cu(II) with the solid chitosan. The sorption was reversible, so the raw chitosan under study can be used as a high loading capacity carrier capable of the sorption and subsequent conditional liberation of a considerable amount of Cu(II) ions.

Absorption↗